IRMPD spectroscopy and quantum-chemical simulations of the reaction products of cisplatin with the dipeptide CysGly

Abstract

The inorganic antineoplastic drug cisplatin was made to react in solution with the dipeptide cysteinylglycine (CysGly), chosen as a functional model of glutathione, and the reaction products were analyzed using electrospray ionization mass spectrometry (ESI-MS). Selected complexes, i.e., the primary substitution product cis-[PtCl(NH3)2(CysGly)]+ and the chelate cis-[PtCl(NH3)(CysGly)]+, were submitted to IR multiple photon dissociation (IRMPD) spectroscopy obtaining their vibrational features. The experimental IR ion spectra were compared with the calculated IR absorptions of different plausible isomeric families, finding CysGly to bind preferentially platinum(II) via its deprotonated thiolic group in the monovalent complex, cis-[PtCl(NH3)2(CysGly)]+, and to evolve in the S,N-bound chelate structure cis-[PtCl(NH3)(CysGly)]+ through the SH and NH2 functionality of the cysteine residue. Moreover, our findings indicate that the platination reaction does not affect the CysGly peptide bond, which remains in its trans configuration.These results provide additional insights into the reactivity of Pt(II)-complexes with glutathione which is involved in cellular cisplatin resistance.